Possible involvement of TGF‑β‑SMAD‑mediated epithelial‑mesenchymal transition in pro‑metastatic property of PAX6

Abstract

Paired box 6 (PAX6) is a transcription factor that has oncogenic features. In breast cancer, PAX6 facilitates tumor progression; however, the underlying mechanism is largely unknown. The majority of breast cancer-related mortalities are associated with metastasis of cancer cells. Therefore, the present study aimed to investigate the role of PAX6 in breast tumor metastasis. PAX6 was stably overexpressed in breast cancer cells to perform tumor migration and metastasis assays in vitro and in vivo. In addition, the expression of PAX6 and transforming growth factor β (TGF-β)-SMAD signaling associated proteins on human breast cancer tissue array, as well as key factors involved in epithelial-mesenchymal transition (EMT) were assayed to explore the mechanism underlying metastasis of breast cancer cells. The expression levels of PAX6 were demonstrated to be increased in human breast cancer tissues and associated with poor clinical outcomes. Overexpression of PAX6 markedly promoted metastasis. Further investigation revealed that PAX6 overexpression increased TGF-β-SMAD signaling pathway and induced EMT. These results suggested that highly expressed PAX6 led to EMT through TGF-β-SMAD signaling pathway, thereby promoting cell metastasis and ultimately affecting survival in patients with breast cancer. Taken together, findings indicated that PAX6 may serve as a therapeutic target for the clinical treatment of breast cancer and the underlying mechanism could be used to overcome metastasis of cancer cells.

Unilateral zebrafish corneal injury induces bilateral cell plasticity supporting wound closure

“…Our transcriptomic analysis (Fig. 8 B) identified another factor regulated by TGF-beta signaling, and essential for eye formation, namely pax6 46 . The zebrafish genome houses two Pax6 genes, among which only Pax6a plays a role in the ocular tissues, while Pax6b is mainly found in the pancreas 47 .…”

The clinical significance of preoperative serum fibrinogen levels and platelet counts in patients with Gallbladder carcinoma

“…Platelets enhance tumor metastasis by expressing immunoregulatory proteins, such as the glucocorticoid induced TNF-related protein to protect tumor cells from the innate immune system [39,40]. Furthermore, A recent study demonstrated that the interactions between platelets and tumor cells facilitated metastasis by promoting epithelial mesenchymal transition through the TGFB/SMAD and NFKB pathways.They also found that inhibition of these two pathways solely could suppress metastasis in vivo [41].…”

Exosomal circular RNA hsa_circ_007293 promotes proliferation, migration, invasion, and epithelial–mesenchymal transition of papillary thyroid carcinoma cells through regulation of the microRNA-653-5p/paired box 6 axis

“…PAX6 belongs to the PAX family and is a vital transcription factor in a variety of biological processes [ 42 ]. Other investigations have also supported PAX6 as an oncogene and have characterized its overexpression across numerous types of human cancers [ 43 , 44 ]. Moreover, its cancer-promoting effects can be regulated by miRNAs [ 43 , 45 , 46 ].…”